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Closed-loop automated drug infusion regulator: A clinically translatable, closed-loop drug delivery system for personalized drug dosing.
DeRidder, Louis B; Hare, Kyle A; Lopes, Aaron; Jenkins, Josh; Fitzgerald, Nina; MacPherson, Emmeline; Fabian, Niora; Morimoto, Josh; Chu, Jacqueline N; Kirtane, Ameya R; Madani, Wiam; Ishida, Keiko; Kuosmanen, Johannes L P; Zecharias, Naomi; Colangelo, Christopher M; Huang, Hen-Wei; Chilekwa, Makaya; Lal, Nikhil B; Srinivasan, Shriya S; Hayward, Alison M; Wolpin, Brian M; Trumper, David; Quast, Troy; Rubinson, Douglas A; Langer, Robert; Traverso, Giovanni.
Affiliation
  • DeRidder LB; Harvard-MIT Division of Health Science Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Mechanical Engineering, Massachusetts Institute
  • Hare KA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Lopes A; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Jenkins J; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Fitzgerald N; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • MacPherson E; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Fabian N; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Comparative Medicine, Massachusetts Institute of Technology, Ca
  • Morimoto J; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Chu JN; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard Medical School, Boston, MA 02115, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Kirtane AR; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Madani W; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Ishida K; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women'
  • Kuosmanen JLP; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Zecharias N; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology
  • Colangelo CM; Agilent Technologies, Lexington, MA 02421, USA.
  • Huang HW; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women'
  • Chilekwa M; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Lal NB; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; MIT Media Lab, Massachusetts Institute of Technology, Cambridge
  • Srinivasan SS; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Hayward AM; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women'
  • Wolpin BM; Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Trumper D; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Quast T; College of Public Health, University of South Florida, Tampa, FL 33612, USA.
  • Rubinson DA; Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Langer R; Harvard-MIT Division of Health Science Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of
  • Traverso G; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women'
Med ; 5(7): 780-796.e10, 2024 Jul 12.
Article in En | MEDLINE | ID: mdl-38663403
ABSTRACT

BACKGROUND:

Dosing of chemotherapies is often calculated according to the weight and/or height of the patient or equations derived from these, such as body surface area (BSA). Such calculations fail to capture intra- and interindividual pharmacokinetic variation, which can lead to order of magnitude variations in systemic chemotherapy levels and thus under- or overdosing of patients.

METHODS:

We designed and developed a closed-loop drug delivery system that can dynamically adjust its infusion rate to the patient to reach and maintain the drug's target concentration, regardless of a patient's pharmacokinetics (PK).

FINDINGS:

We demonstrate that closed-loop automated drug infusion regulator (CLAUDIA) can control the concentration of 5-fluorouracil (5-FU) in rabbits according to a range of concentration-time profiles (which could be useful in chronomodulated chemotherapy) and over a range of PK conditions that mimic the PK variability observed clinically. In one set of experiments, BSA-based dosing resulted in a concentration 7 times above the target range, while CLAUDIA keeps the concentration of 5-FU in or near the targeted range. Further, we demonstrate that CLAUDIA is cost effective compared to BSA-based dosing.

CONCLUSIONS:

We anticipate that CLAUDIA could be rapidly translated to the clinic to enable physicians to control the plasma concentration of chemotherapy in their patients.

FUNDING:

This work was supported by MIT's Karl van Tassel (1925) Career Development Professorship and Department of Mechanical Engineering and the Bridge Project, a partnership between the Koch Institute for Integrative Cancer Research at MIT and the Dana-Farber/Harvard Cancer Center.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Drug Delivery Systems / Precision Medicine / Fluorouracil Limits: Animals / Humans Language: En Journal: Med Year: 2024 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Drug Delivery Systems / Precision Medicine / Fluorouracil Limits: Animals / Humans Language: En Journal: Med Year: 2024 Document type: Article